Abstract: FR-PO751

Unbiased Screening of Urinary Protein Biomarkers for Glomerular Filtration Rate Normalization

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Soomro, Sanam, University of Houston, Houston, Texas, United States
  • Stanley, Samantha, University of Houston, Houston, Texas, United States
  • Saxena, Ramesh, University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Petri, Michelle, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Mohan, Chandra, Univ Houston, Houston, Texas, United States
Background

To account for glomerular filtration rate, urinary creatinine is routinely used for the normalization of urine biomarkers related to disease. Because of the small size of this metabolite, antibodies are difficult and expensive to develop, limiting the applications of disease-specific urine protein biomarkers for antibody-based point of care applications.

Methods

An aptamer-based screening of 1129 proteins in 24 human urine samples (8 active lupus nephritis (LN), 8 inactive LN, 8 healthy controls (HC)) was carried out to identify urine proteins that correlated well with urine creatinine but not disease.

Results

The screen uncovered 18 proteins that correlated well with urinary creatinine but were similar in patients with or without nephritis. Further validation in an independent cohort of 48 subjects (16 active LN, 16 inactive LN, 16 HC) showed a significant positive correlation of urine HVEM, RELT, and Dectin-1 to urinary creatinine. The most promising marker, urine HVEM, was significantly correlated to urinary creatinine in both white (Pearson r = 0.7229, P = 0.0001) and black subjects (Pearson r = 0.6111, P = 0.0009). Finally, normalization of other urinary biomarker proteins against urine HVEM showed comparable fold change and statistical significance as normalization to urinary creatinine.

Conclusion

Instead of the metabolite creatinine, proteins such as HVEM, RELT, and Dectin-1 can be used for normalization of urine biomarkers. The use of proteins instead of metabolites for normalization paves the way towards novel diagnostic approaches.

Urine HVEM, RELT, and Dectin-1 were validated by ELISA and found to be significantly correlated with urinary creatinine. HVEM, the most promising marker for GFR normalization, was also used to normalize ALCAM, a biomarker for SLE, to have comparable fold change and statistical significance as normalization to urinary creatinine.